A lack of neutralizing antibodies distinguishes HIV-1 from most other viral pathogens and is responsible to a large degree for the ability of HIV-1 to maintain a persistent infection. A few monoclonal antibodies have been isolated that are broadly neutralizing. We have used X-ray crystallography to investigate the epitopes of broadly neutralizing antibodies and their mechanisms of neutralization. In particular, we have examined CD4-binding-site directed antibodies like VRC01, V1/V2-directed antibodies like PG9 and PG16, and membrane-proximal-binding antibodies like 2F5. The VRC01 antibody is particularly attractive as it neutralizes over 90% of circulating HIV-1 isolates and appears to be elicited in high titer in 5-10% of HIV-1 infected individuals. The V1/V2-directed antibodies are also attractive, as some estimate that this is the most commonly elicited broadly neutralizing response.